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Stem Cells Coaxed To Create Working Blood Vessels

Scientists directed human stem cells to form networks of tiny
blood vessels that can connect to the existing circulation in mice.
The finding might assist future efforts to repair and regenerate
tissues and organs, which need an adequate blood supply to grow
and survive.

Blood flow is essential for just about every part of the body.
Blood brings oxygen and nutrients to cells, carries away waste
products and performs countless other functions. To create blood
flow where it’s needed, researchers have been exploring ways
to make lab-grown blood vessels that can be transplanted into the
body. Earlier studies have found that the endothelial cells that
line the inside of blood vessels can naturally assemble into vascular
networks. But these tiny blood vessels, or microvessels, deteriorate
without the presence of supporting cells called pericytes.

Some research groups are working with pluripotent stem cells, which have the
potential to transform into any cell type in the body. They’ve found ways
to direct the stem cells to become specific cell types, including pericytes and
endothelial cells. But the process is complex, requiring multiple rounds of cell
sorting and purification. Some scientists have tried growing distinct sets of
precursor cells in the protein scaffolds of “decellularized” blood
vessels. To date, though, many of these efforts have been inefficient and difficult
to translate for clinical use.

In hopes of simplifying the process, Dr. Sharon Gerecht and her colleagues at
Johns Hopkins University aimed to take advantage of the natural ability of endothelial
cells to self-assemble into vascular networks. Their research was supported in
part by NIH’s National Heart, Lung and Blood Institute (NHLBI) and National
Cancer Institute (NCI). Their results were published in the July 30, 2013, issue
of the Proceedings of the National Academy of Sciences.

The scientists first devised a way to use chemical cues to guide human pluripotent
stem cells to form a specialized population made up of just 2 types of vascular
cells. This bicellular population could only mature into pericytes and
endothelial cells. “It makes the process quicker and more robust if you
don't have to sort through a lot of cells you don't need to find the ones you
do, or grow 2 batches of cells,” says Sravanti Kusuma, who developed the
method.

The scientists next grew the bicellular population in a 3-D hydrogel matrix—a
clear, mesh-like gel that mimics the environment inside the body. Within days,
complex networks of hollow vascular tubes appeared, including both endothelial
cells and pericytes.

To see how the cells would behave within the body, the scientists implanted the
gel-encased microvascular networks into mice. By 2 weeks, the implanted cells
and vessels had become connected to the mouse circulatory system and allowed
blood flow. The researchers, though, note that additional studies are needed
to fine-tune the process before it can be tested in humans.

“In demonstrating the ability to rebuild a microvascular bed in a clinically
relevant manner, we have made an important step toward the construction of blood
vessels for therapeutic use,” says Gerecht. “Our findings could yield
more effective treatments for patients afflicted with burns, diabetic complications
and other conditions in which vasculature function is compromised.”